Trophic influences of human and rat amniotic fluid on neural tube-derived rat fetal cells.

Normal human (week 17-20) and rat (E16-17) amniotic fluids were used as culture media for primary cultures of rat fetal (E 16) cortical, mesencephalic and striatal cell dissociates, or astroglial subcultures from the same brain regions. Phase-bright and dark cells were identified under phase contrast microscopy and their cell processes were measured utilizing semi-automated procedures. Subcultured astroglia were immuno-reacted against glial fibrillary acidic protein and fibronectin. Rat and human amniotic fluid allowed survival and growth of neuronal and non-neuronal cells. Human amniotic fluid samples were trophic in variable degrees. Cerebral cortex subcultured astroglia usually expressed a radial-like morphotype. Although charcoal-adsorbed human amniotic fluid was trophic for primary cultures, its ability to sustain neuritic growth depended on its degree of trophism before treatment. Growth of cell processes in neuronal- and glial-like cells in primary cultures was inhibited to different degrees by the addition of antisera towards nerve or epidermal growth factors. It is concluded that amniotic fluid constitutes a trophic medium for astroglia and neurons. Both, nerve and epidermal growth factors appear to be necessary for growth of cell processes in neuronal and glial primary cultures in amniotic fluid. Trophic effect of amniotic fluid on subcultured astroglia did not seem to be diminished by nerve growth factor antiserum. The role of amniotic fluid during the early phases of brain organogenesis is discussed.

Effect of long-term oral nisoldipine on infarct size and collateral development in pigs undergoing gradual occlusion of the left circumflex artery.

We examined the effects of nisoldipine on infarct size and collateral development in pigs, whose coronary circulation is similar to that of humans, using an experimental protocol reproducing as closely as possible the usual clinical setting. Fifteen pigs undergoing left circumflex Ameroid-occlusion were randomized into a control group (n = 8) and a group (n = 7) treated with oral nisoldipine 0.03 mg/kg every 6 h for 1 month starting on the second postoperative day. Infarct size (tetrazolium red) was 37.2 +/- 9.2% of the circumflex distribution in the control group and 10 +/- 3.2% in the treated group (p less than 0.01). Endocardial and transmural blood flows (microspheres) in the circumflex distribution were significantly higher (p less than 0.05) in the treated group (control endocardial 1.25 +/- 0.1 mg/g/min, treated endocardial 1.77 +/- 0.26 ml/g/min; control transmural 1.39 +/- 0.08 ml/g/min; treated transmural 1.78 +/- 0.23 ml/g/min). Epicardial flow and the ratio of subendocardial to subepicardial blood flow (endo/epi) were nonsignificantly higher in treated pigs. No differences were observed in heart rate (HR) and aortic pressure (AP). We conclude that in pigs undergoing left circumflex Ameroid-occlusion, long-term oral nisoldipine reduces infarct size and enhances collateral circulation to the ischemic myocardium.

The effect of the new calcium antagonist nisoldipine (BAY k-5552) on myocardial infarct size limitation in conscious dogs.

The effect of the new calcium antagonist nisoldipine (BAY k-5552) on myocardial infarct size was studied in four groups of conscious dogs undergoing acute left anterior descending coronary artery occlusion. Group I received placebo for 48 hours before and for 24 hours after occlusion; group II received placebo before and nisoldipine (0.3 mg/kg orally every 6 hours) after occlusion; group III received nisoldipine before and placebo after occlusion; and group IV received nisoldipine before and after occlusion. Infarct size was quantified with the tetrazolium red staining technique. Infarcted ventricular mass was 24.5 +/- 6.6% (mean +/- SD) for group I (control), 21.4 +/- 4.4% for group II (p = NS against control), 13.9 +/- 4.5% for group III (p less than 0.05), and 14.1 +/- 4.0% for group IV (p less than 0.05). Post occlusion sudden death was 30% in non-pretreated dogs and 0% in pretreated dogs (p less than 0.001). We conclude that prophylactic oral treatment with nisoldipine decreases infarct size and lowers the incidence of sudden death in conscious dogs undergoing acute coronary occlusion.

Sensitivity of enzymatic release due to ischemia in the isolated rat heart.

The sensitivity of cardiac enzymes (GOT, a-HBDH, LDH, LDH-1, CPK and CPK-MB) was studied in the isolated rat heart subjected to 0 (non-ischemic), 20, 30 and 40 min of total global ischemia (0 ml/min) followed by reperfusion in which three consecutive perfusate samples were collected for enzymatic measurements. Cardiac function, estimated by peak tension (Tp), maximal rate of tension development (Tc) and relaxation (Tr) decreased to 0 with ischemia and recovered with reperfusion to 100% in the 20 min, 50% in the 30 min and 10% in the 40 min ischemic groups. In these three groups, enzymatic release, measured as the relative increment (RI) with respect to the control samples, gave significantly higher values than those of non-ischemic hearts (P less than 0.001). LDH-1 was the most sensitive enzyme (P less than 0.0005) for the detection of ischemia in these experimental conditions.

Sensitivity of enzymatic release due to ischemia in the isolated rat heart.

The sensitivity of cardiac enzymes (GOT, a-HBDH, LDH, LDH-1, CPK and CPK-MB) was studied in the isolated rat heart subjected to 0 (non-ischemic), 20, 30 and 40 min of total global ischemia (0 ml/min) followed by reperfusion in which three consecutive perfusate samples were collected for enzymatic measurements. Cardiac function, estimated by peak tension (Tp), maximal rate of tension development (Tc) and relaxation (Tr) decreased to 0 with ischemia and recovered with reperfusion to 100

in the 20 min, 50

in the 30 min and 10

in the 40 min ischemic groups. In these three groups, enzymatic release, measured as the relative increment (RI) with respect to the control samples, gave significantly higher values than those of non-ischemic hearts (P less than 0.001). LDH-1 was the most sensitive enzyme (P less than 0.0005) for the detection of ischemia in these experimental conditions.

Myocardial triglycerides increased by fasting. Effects of hypoxia on contractility and enzymatic release.

The effect of fasting on the mechanics of contraction was studied in the isolated perfused rat heart, in oxygenated and hypoxic conditions. Animals were subjected to 48 h of fasting, a condition which produces augmented endogenous triglycerides (TG). Normal and fasted rats were submitted to a 10-min period of hypoxia, which depressed peak tension (Tp), maximal rate of contraction (Tc), and relaxation (Tr); all three parameters recovered with reoxygenation. However, Tp and Tc of hearts of fasted animals were less affected by hypoxia, and Tp, Tc, and Tr attained higher levels during reoxygenation compared with hearts of normally fed animals. These results suggest that as triglycerides are augmented, they might have a beneficial action on the hypoxic heart, though other unknown effects of fasting cannot be discarded. LDH was the only cardiac enzyme whose release in the perfusion medium significantly increased in hypoxic hearts, irrespective of the fasting state of the animal. The positive correlation between LDH and an index of relative recovery (IH) for Tp, Tc, and Tr, indicate that not only hypoxia but a good recovery are necessary to yield high LDH values.